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About the Regulatory Profession

The regulatory function is vital in making safe and effective healthcare products available worldwide. Individuals who ensure regulatory compliance and prepare submissions, as well as those whose main job function is clinical affairs or quality assurance are all considered regulatory professionals.

Regulatory Code of Ethics

One of our most valuable contributions to the profession is the Regulatory Code of Ethics. The Code of Ethics provides regulatory professionals with core values that hold them to the highest standards of professional conduct.

Regulatory Competency Framework

Like all professions, regulatory is based on a shared set of competencies. The Regulatory Competency Framework describes the essential elements of what is required of regulatory professionals at four major career and professional levels.

Regulatory Convergence

Join the brightest minds in regulatory at the annual Regulatory Convergence. See the global regulatory community in action. Intensive workshops. Topical sessions. Meet ups with regulators. This is where it all comes together.

New Report Investigates Drivers of Off-Label Prescribing in the EU

A lack of incentives to go through the marketing authorization process to extend certain drug labels, as well as pricing and reimbursement issues, were cited as some of the varied drivers of off-label prescription drug use in the EU, according to a new report from the European Commission.

“Data from scientific literature reveal that the prevalence of off-label use in the EU within the paediatric population is generally high, covers a broad range of therapeutic areas and is common practice for many prescribers in both the hospital and the outpatient settings,” the report says. “Thirty-two studies which took place in various paediatric populations within a hospital setting (covering data from 16 EU Member States) showed that a range of 13-69% of the prescriptions investigated was off-label. In forty studies in the outpatient setting (covering data from 12 Member States) there was a range of 2-100%.”

The report notes a similar pattern in adult populations: 23 studies in various adult inpatient populations (covering data from six Member States) showed that a range of 7-95% of the prescriptions investigated were used off-label. In 13 outpatient studies (also data from six Member States) a range of 6-72% was found.

“Variation in off-label prevalence is not only observed between but also within countries, depending for example on the methodology used and the population studied. A comparison of prevalence figures between the various EU Member States is therefore not possible, but it is apparent that the majority of, if not all, EU Member States are faced with off-label use of medicinal products to some extent,” the report says.

Policy Tools

As far as the reasons for off-label uses, the report points to literature and patients, health professionals and the pharmaceutical industry noting “limited incentives” to extend the labelling of existing medicines, “especially for off-patent products. Literature and stakeholders (regulatory, reimbursement, patients) also mention the increase in requirements for marketing authorisation over the years as well as the sometimes long development times and high costs to investigate a new indication.”

And in some Member States products are not available due to economic reasons, while, “Another factor frequently mentioned (by regulatory representatives, patients, [healthcare professionals] HCPs and pharmaceutical industry) was pricing and reimbursement. An important driver on a patient and HCP level is the fact that there is sometimes no other choice than prescribing off-label (mentioned in literature and all stakeholder groups).”

Examples of policy tools EU Member States use to deal with off-label prescribing include:

Temporary recommendations for use and permission to prescribe off-label, such as the “temporary recommendations for use (RTU) scheme” in France and the Hungarian system where prescribers or their organizations have to ask for permission to prescribe a product off-label.

Measures to regulate reimbursement: France and Italy explicitly allow for reimbursement of off-label use and also when on-label, authorized or not strictly identical alternatives exist.

Policy tools providing guidance for prescribers such as the UK’s 2013 General Medical Council Guidance, which offers good practices in prescribing and managing medicines and devices

Professional standards, such as in the Netherlands where off-label prescribing is only allowed if the relevant professional body has developed protocols or professional standards on particular off-label use.

Patient-focused policy tools, for example requiring informed consent, or for serious interventions, upon request of the patient, a health professional has to register what intervention the patient has given consent, which occurs in the Netherlands.

In Member States without specific policies on off-label use, “the dominant view is that off-label use is an issue to be dealt with at the level of the prescriber rather than at the regulatory or healthcare system level. Prescribers are trusted to know what is best for the well-being of the patient, with the medical need of the patient leading their decisions. Yet, it is also mentioned that lack of clarity about the liability is an issue in case of off-label prescribing and that patients should be properly informed and provide consent.”

Therapeutic Areas

In terms of particular therapeutic areas seeing more off-label uses than others, the report says the literature data “reveal that off-label use stretches along a wide variety of areas, with special emphasis for children on cardiovascular diseases (e.g. the use of antihypertensives), infectious disease (e.g. anti-bacterial agents), central nervous system (e.g. analgesic agents, psychiatry medication), respiratory system (e.g. asthma medicines), and alimentary tract and metabolism drugs (e.g. reflux medicines).”

For adults, the most frequent areas were oncology, rheumatology, immunology and psychiatry, the report says.

The report also offers the example of Avastin (bevacizumab) versus Lucentis (ranibizumab), noting the driver for off-label use of Avastin in the treatment of wet age-related macular degeneration “changed in time from unavailability of an alternative to better efficacy of the unregistered medicine compared to the registered one, and then to the product with lowest costs. This analysis of the drivers shows that off-label use of medicines is driven by many factors. These drivers vary per type of medicines and even within a certain type the drivers may vary over time.”

Industry group EFPIA welcomed the report in a statement: “Whilst we accept that off-label medicines can be prescribed by physicians to address a patient’s concrete medical needs with his or her consent, we strictly oppose the promotion of off-label use for economic reasons which contradicts the EU principle that the protection of public health must unquestionably take precedence over economic considerations.”

The report also includes breakdowns of Member State off-label policy frameworks.